The invention relates to an immunoassay of propranolol and more particularly to new chemical compounds which are derivatives of propranolol and which are useful in immunoassay applications.
Propranolol is among the most widely prescribed prescription drugs in the world and is also the subject of extensive research worldwide. Propranolol is a beta-adrenergic receptor blocking drug. It specifically competes with beta-adrenergic receptor stimulants for available beta receptor sites.
Propranolol is prescribed primarily for the treatment of hypertension, angina pectoris and arrhythmia. The objective of propranolol therapy is to decrease adverse sympathetic stimulation, but not to the degree that may impair necessary sympathetic support and possibly precipitate heart failure.
One of the major problems involved in prescribing propranolol is determining the proper dosage requirement for a patient. While the desirable concentration of propranolol in the patient's blood is known, it has been found that the uptake of this drug by most patients is variable, so that one has no assurance that a particular dose of propranolol administered to the patient will produce the desired concentration in the blood. Attaining the optimal dose is important in achieving maximal therapeutic benefit and in avoiding potentially serious side effects.
Due to its extensive metabolism and its lack of appropriate functional groups which might be used to conjugate it to a protein carrier, the only generally useful method for the analysis of propranolol in body fluids is gas chromatography-mass spectrometry (GC-MS). Because the GC-MS method is both highly complex and expensive, it has not attained routine clinical use.
There have been published reports of radioimmunoassays for propranolol, but these assays suffer from unacceptably high cross reactivity with inactive propranolol metabolites frequently encountered in biological samples. This cross reactivity is the result of using the propranolol side chain nitrogen as the point of attachment to the protein carrier. The antibodies generated by these compounds recognize the ring end of the propranolol molecule which is common to many of the inactive metabolites.
Accordingly, it is a principal object of the present invention to provide new derivatives of propranolol which can be used to prepare antibodies to propranolol that recognize the side chain end of the propranolol molecule.
It is another object of the present invention to provide new derivatives of propranolol which can be conjugated to a tracer moiety for use in immunoassay applications.
It is a further object of the present invention to provide a highly sensitive and specific immunoassay of propranolol.
It is still a further object of the present invention to provide an immunoassay of propranolol which is significantly simpler and less expensive than the GC-MS method.